The present invention relates to the use of quinolone carboxylic acid formulations in the treatment of ocular and periocular infections. The present invention also relates to sustained release compositions comprising specific quinolone carboxylic acid compounds in a vehicle that permits administration in drop form. The invention also relates to quinolone carboxylic acid compositions and methods of preparing the same.
Treatment of ocular and periocular infections can be effected by the application of ointments or the instillation of topical antibiotic suspensions to the eye. Such compositions can employ, for example, one or more of the following antibiotic agents: neomycin, polymixin B, bacitracin, trimethoprim, tobramycin, terramycin, sulfacetamide (e.g., CORTICOSPORIN(trademark), Monarch Pharmaceuticals, Bristol, Tenn.; NEODECADRON(trademark), Merck and Co., West Point, Pa.; POLYSPORIN(trademark), Glaxo Wellcome Inc., Research Triangle Park, N.C.; POLYTRIM(trademark) AND BLEPHAMIDE(trademark), Allergan Inc., Irvine, Calif.; TOBRADEX(trademark), Alcon Laboratories, Fortworth, Tex.; TERA-COTRIL(trademark), Pfizer Inc., New York, N.Y. etc.). Compositions such as: CHIBOXIN(trademark) (Merck and Co., West Point, Pa.), CILOXAN(trademark) (Alcon Laboratories, Fortworth, Tex.) and OCUFLOX(trademark) (Allergan Inc., Irvine, Calif.) employ quinolone antimicrobials in aqueous solution or aqueous suspension.
As in the topical administration of other medicaments to the eye, the delivery of antimicrobial agents is influenced by a variety of factors, among them comfort, consistency and accuracy of dosage, type and time of any vision interference, ease of administration, and timing of delivery. These factors have been discussed, for example, in Davis et al., U.S. Pat. No. 5,192,536.
While the art has produced a variety of compositions for the treatment of ocular and periocular infections, there is still a need for broad-spectrum antimicrobial compositions with the characteristics of high bioavailabity and adsorption. Such compositions would be even more desirable provided they comprise a vehicle that readily permits accurate administration of dosages in a convenient form such as drops. It is also desirable that the composition be non-irritating and soothing to already irritated ocular and periocular tissues. The aforementioned compositions are even more desirable when they also provide sustained release of the antimicrobial compositions and are not subject to rapid dilution or rapid removal of the antibiotics by lacrimation.
There is a need in the art for topically applied anti-microbial agents and compositions useful in their administration.
The present invention includes and provides a topical ophthalmic composition comprising a quinolone carboxylic acid derivative of formula (I), 
wherein R1 is a hydrogen atom, an alkyl group, an aralkyl group, an ester residual group which can be hydrolyzed in vivo, R2 is a hydrogen atom or an amino group which may be substituted by one or two lower alkyl groups, X is a hydrogen atom or a halogen atom, Y is CH2, O, S, SO, SO2, or Nxe2x80x94R3, wherein R3 is a hydrogen atom or a lower alkyl group, and Z is an oxygen atom or two hydrogen atoms.
The present invention includes and provides a method of treating or preventing an infection in the ocular or periocular region comprising: delivering to the ocular or periocular region a composition comprising a quinolone carboxylic acid derivative of formula (I), 
wherein R1 is a hydrogen atom, an alkyl group, an aralkyl group, an ester residual group which can be hydrolyzed in vivo, R2 is a hydrogen atom or an amino group which may be substituted by one or two lower alkyl groups, X is a hydrogen atom or a halogen atom, Y is CH2, O, S, SO, SO2, or Nxe2x80x94R3, wherein R3 is a hydrogen atom or a lower alkyl group, and Z is an oxygen atom or two hydrogen atoms.
The present invention includes and provides a method of preparing a sustained release topical ophthalmic delivery system, comprising: preparing an composition comprising a quinolone carboxylic acid derivative of formula (I), 
wherein R1 is a hydrogen atom, an alkyl group, an aralkyl group, an ester residual group which can be hydrolyzed in vivo, R2 is a hydrogen atom or an amino group which may be substituted by one or two lower alkyl groups, X is a hydrogen atom or a halogen atom, Y is CH2, O, S, SO, SO2, or Nxe2x80x94R3, wherein R3 is a hydrogen atom or a lower alkyl group, and Z is an oxygen atom or two hydrogen atoms; and, packaging said composition for administration to the eye.